Oocyte-derived BMP15 and FGFs cooperate to promote glycolysis in cumulus cells

Sugiura, Koji; Su, You-Qiang; Diaz, Francisco J.; Pangas, Stephanie A.; Sharma, Shweta; Wigglesworth, Karen; O’Brien, Marilyn J.; Matzuk, Martin M.; Shimasaki, Shunichi; Eppig, John J.

doi:10.1242/dev.020024

Cited by 87 publications

(134 citation statements)

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“…Oocyte quality is assured by LH-driven nutritional and informational signals emanating in cumulus cells [2,36] and, at the same time, oocyte-derived factors influence GC functions such as cumulus expansion, apoptosis, carbohydrate metabolism and steroidogenesis [53,54] influencing their own microenvironment. Oocyte secretes GDF9, a TGF-β superfamily member that is required for normal folliculogenesis in mouse [15,59].…”

Section: Discussionmentioning

confidence: 99%

Follicular fluid hormonal profile and cumulus cell gene expression in controlled ovarian hyperstimulation with recombinant FSH: effects of recombinant LH administration

Barberi

Ermini

Morelli

et al. 2012

J Assist Reprod Genet

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Purpose Down-regulation with gonadodropin-releasing agonist (GnRH-a) protocol during IVF stimulation leads to a severe endogenous LH suppression, which may affect the follicular development. The aim of the study was to evaluate the effects of recombinant LH (r-LH) administration, during late follicular development stages, in recombinant FSH (r-FSH) stimulated cycles on follicular fluid (FF) parameters and on cumulus cell quality. Methods Twenty patients undergoing IVF were stimulated in a long GnRH agonist protocol with r-FSH alone or with r-LH supplementation when the leading follicle reached diameter of 14 mm. FF was collected at the time of oocyte retrieval from 32 follicles ≥ 18 mm. Serum FSH, LH, estradiol (E 2 ), and progesterone (P 4 ) were evaluated on the day of hCG administration. Intra-follicular E 2 , P 4 , AMH and TGF-β were assayed. Total RNA from 18 individual cumuli was isolated for gene expression analyses. Results R-LH increased FF P 4 levels. FF TGF-β levels and PTGS2 and HAS2 expression in cumulus cells (CCs) positively correlated with increased P 4 levels observed in FFs, while a negative correlation was found between P 4 and AMH levels. Conclusions FF positive correlation between P 4 and TGF-β levels and CC expression of PTGS2 and HAS2 suggest an association with a better follicle quality. In addition, our data suggest that late follicular phase r-LH supplementation leads to a more advanced stage of follicular maturation.

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Section: Discussionmentioning

confidence: 99%

Follicular fluid hormonal profile and cumulus cell gene expression in controlled ovarian hyperstimulation with recombinant FSH: effects of recombinant LH administration

Barberi

Ermini

Morelli

et al. 2012

J Assist Reprod Genet

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“…These findings indicated that FoxO3a/BMP15 signaling may be an important mechanism that regulates follicular development. Notably, previous studies have demonstrated that BMP15 regulates Smad1/5/8 activity and its regulatory effect on ovarian follicular development (22)(23)(24). Thus, the present study investigated Smad1/5/8 activity and demonstrated that HFD significantly reduced the level of p-Smad1/5/8.…”

Section: Discussionmentioning

confidence: 99%

“…BMPs bind to their cell membrane receptor and exert their effects through receptor-mediated activation of Smad transcription factors (21). Previous studies have demonstrated that BMP15 regulates Smad1/5/8 activity and regulates ovarian follicular development (22)(23)(24). Additionally, Liu et al (11,25) reported that constitutively active FoxO3a expressed in oocytes stimulated downregulation of BMP15 expression and suppressed Smad pathway activation.…”

Section: Introductionmentioning

confidence: 99%

Effect of high-fat diet-induced obesity on the Akt/FoxO/Smad signaling pathway and the follicular development of the mouse ovary

Zhang

Liao

et al. 2016

Molecular Medicine Reports

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Abstract. Obesity has a negative effect on ovarian functions, which is reported to increase the risk of infertility. The mechanism underlying obesity-induced infertility is not yet clear. The present study established a high-fat diet (HFD)-induced obesity mouse model to elucidate the mechanisms underlying the effect of HFD-induced obesity on follicular development in the mouse ovary. The 4-week-old female mice were fed with HFD or normal control (NC) diet for 15 or 20 weeks. Body mass index was used to demonstrate that the mice were obese following HFD treatment. The follicular development of the ovaries from the HFD group mice was retarded in a time-dependent manner, as demonstrated by morphological and histological examination of the ovaries. Further investigation via western blot analysis demonstrated that the activity of the transcription factor, forkhead box O3a (FoxO3a), was increased by HFD through downregulated FoxO3a phosphorylation, which may contribute to the inhibited development of ovarian follicles. To determine the regulatory mechanism of FoxO3 on the follicular development, the expression levels of FoxO3a target protein, Smad1/5/8, were also determined and there was significant decrease in phosphorylated Smad1/5/8 in the ovaries from the HFD group compared with the NC group, indicating that FoxO3a/Smad1/5/8 may be important in the regulation of follicular development. The expression levels of the upstream regulator of FoxO3a, Akt, were also examined and it was demonstrated that Akt phosphorylation was significantly reduced in the HFD group compared with the NC group, indicating that Akt/FoxO3a may be also involved in follicular development. Together, the experiments demonstrated that HFD-induced obesity affected the activity of the Akt/FoxO3a/Smad1/5/8 signaling pathway in a time-dependent manner during the follicular development of the mouse ovary, leading to abnormal follicular development. These findings may provide part of a theoretical basis for the clinical prevention and treatment of obesity-associated female infertility.

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“…Another class of paracrine-acting factors that have received recent attention for their abilities to control follicular development and oocyte maturation are the fibroblast growth factors (FGFs). FGFs had been found to play crucial roles in folliculogenesis, including primordial follicle activation and regulation of granulosa and cumulus cell mitosis, apoptosis and glycolysis (Sugiura et al 2007). Several other FGFs were found to be produced in oocytes and follicular somatic cells of cattle (Parrott and Skinner 1998), mice (Sugiura et al 2007) and human (Ben-Haroush et al 2005).…”

Section: Introductionmentioning

confidence: 99%

“…FGFs had been found to play crucial roles in folliculogenesis, including primordial follicle activation and regulation of granulosa and cumulus cell mitosis, apoptosis and glycolysis (Sugiura et al 2007). Several other FGFs were found to be produced in oocytes and follicular somatic cells of cattle (Parrott and Skinner 1998), mice (Sugiura et al 2007) and human (Ben-Haroush et al 2005). In mice, FGF4 originated from inner cell mass inhibited the differentiation of trophectoderm (Feldman et al 1995).…”

Section: Introductionmentioning

confidence: 99%

Effect of Fibroblast Growth Factor 2 (FGF2) and Insulin Transferrin Selenium (ITS) on In Vitro Maturation, Fertilization and Embryo Development in Sheep

Mondal

Mor

Reddy

et al. 2015

Braz. arch. biol. technol.

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The present study evaluated the effect of fibroblast growth factor 2 (FGF2) and insulin-transferrin-selenium (ITS) to the in vitro maturation and embryo culture media on ovine oocyte maturation, cleavage and embryo development. Oocytes having more than five layers of unexpanded cumulus cells and granular homogenous ooplasm were cultured into 50 μL droplets of eight different culture systems: (i) TCM-199 (Tissue Culture Medium-199); (ii) TCM-199+10 ng/mL FGF2; (iii) TCM-199+20 ng/mL FGF2; (iv) TCM-199+30 ng/mL FGF2; (v) TCM-199+10 ng/mL ITS; (vi) TCM-199+20 ng/mL ITS; (vii) TCM-199+30 ng/mL ITS and (viii) TCM-199+20 ng/mL ITS+20 ng

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Oocyte-derived BMP15 and FGFs cooperate to promote glycolysis in cumulus cells

Cited by 87 publications

References 0 publications

Follicular fluid hormonal profile and cumulus cell gene expression in controlled ovarian hyperstimulation with recombinant FSH: effects of recombinant LH administration

Follicular fluid hormonal profile and cumulus cell gene expression in controlled ovarian hyperstimulation with recombinant FSH: effects of recombinant LH administration

Effect of high-fat diet-induced obesity on the Akt/FoxO/Smad signaling pathway and the follicular development of the mouse ovary

Effect of Fibroblast Growth Factor 2 (FGF2) and Insulin Transferrin Selenium (ITS) on In Vitro Maturation, Fertilization and Embryo Development in Sheep

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